Antiepileptic Drug Interactions - Principles and Clinical Implications
Antiepileptic Drug Interactions - Principles and Clinical Implications
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DOI：
10.2174/157015910792246254
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发表时间：
2010-09-01
影响因子：
5.3
通讯作者：
Landmark, Cecilie Johannessen
中科院分区：
文献类型：
--
作者：
Johannessen, Svein I.;Landmark, Cecilie Johannessen
抗癫痫药物（AEDs）广泛用作癫痫和其他适应症的长期连续治疗或单药治疗，并且由一组高度易受药物相互作用的药物组成。本综述的目的是关注涉及AED的临床相关相互作用，特别是药代动力学相互作用。较旧的AED易于引起诱导（卡马西平、苯巴比妥、苯妥英、扑米酮）或抑制（丙戊酸），分别导致其他AED以及其他药物类别（抗凝剂、口服避孕药、抗抑郁药、抗精神病药、抗微生物药、抗抑郁药和免疫抑制剂）的血清浓度降低或升高。相反，抗抑郁药和抗精神病药中的酶抑制剂、抗微生物药物（如大环内酯类或异烟肼）可增加AED的血清浓度，其他机制如诱导、吸收或排泄减少（如口服避孕药、西咪替丁、丙磺舒和抗酸剂）可降低AED的血清浓度。涉及新型AED的药代动力学相互作用包括酶抑制剂非氨酯、卢非酰胺和司替戊醇以及诱导剂奥卡西平和托吡酯。拉莫三嗪受这些药物、较旧的AED和其他口服避孕药的影响。根据血清浓度变化的临床后果，个体AED相互作用可分为三个水平。这种方法可能指向具有特定重要性的相互作用，但应谨慎实施，因为它并不意味着过度简化事实问题。1级涉及严重的临床后果，应避免联合用药。2级通常意味着谨慎和可能的剂量调整，因为组合可能无法避免。3级是指通常不需要调整剂量的相互作用。关于药物相互作用的最新知识对于预测涉及AED的有害或缺乏作用的可能性非常重要。
Antiepileptic drugs (AEDs) are widely used as long-term adjunctive therapy or as monotherapy in epilepsy and other indications and consist of a group of drugs that are highly susceptible to drug interactions. The purpose of the present review is to focus upon clinically relevant interactions where AEDs are involved and especially on pharmacokinetic interactions. The older AEDs are susceptible to cause induction (carbamazepine, phenobarbital, phenytoin, primidone) or inhibition (valproic acid), resulting in a decrease or increase, respectively, in the serum concentration of other AEDs, as well as other drug classes (anticoagulants, oral contraceptives, antidepressants, antipsychotics, antimicrobal drugs, antineoplastic drugs, and immunosupressants). Conversely, the serum concentrations of AEDs may be increased by enzyme inhibitors among antidepressants and antipsychotics, antimicrobal drugs (as macrolides or isoniazid) and decreased by other mechanisms as induction, reduced absorption or excretion (as oral contraceptives, cimetidine, probenicid and antacides). Pharmacokinetic interactions involving newer AEDs include the enzyme inhibitors felbamate, rufinamide, and stiripentol and the inducers oxcarbazepine and topiramate. Lamotrigine is affected by these drugs, older AEDs and other drug classes as oral contraceptives. Individual AED interactions may be divided into three levels depending on the clinical consequences of alterations in serum concentrations. This approach may point to interactions of specific importance, although it should be implemented with caution, as it is not meant to oversimplify fact matters. Level 1 involves serious clinical consequences, and the combination should be avoided. Level 2 usually implies cautiousness and possible dosage adjustments, as the combination may not be possible to avoid. Level 3 refers to interactions where dosage adjustments are usually not necessary. Updated knowledge regarding drug interactions is important to predict the potential for harmful or lacking effects involving AEDs.